Eureka!

It’s in the Genes

A breast cancer survivor’s hunch leads to a game-changing study

By Patricia Donovan

In 2007, Veronica Meadows-Ray of Buffalo became the sixth of
eight women in her family to be diagnosed with breast cancer.

In her case, it was triple negative breast cancer, an aggressive
and frequently recurring type that is most likely to occur before
the age of 50, in African-American and Hispanic women, and in women
who carry a mutation of the tumor-suppressor gene BRCA1.
Meadows-Ray met the first two of those criteria—she is
African-American and was 47 when diagnosed—but she tested
negative for the BRCA gene. Her one cousin who also underwent
genetic screening also tested negative.

There were no answers to her questions, however. The pioneering
BRCA study, conducted in the 1990s, had found that mutations in the
BRCA1 and 2 genes accounted for 20 to 25 percent of hereditary
breast cancers, and 5 to 10 percent of all breast cancers, in the
study population—but that population was composed of 5,000
women of European heritage. No one had ever conducted a genetic
study of breast cancer in African-American families, despite the
fact that African-American women have the second-highest incidence
of breast cancer in the United States, and the highest rates of
mortality from the disease.

Meadows-Ray is active in the Buffalo/Niagara
Witness Project, one of more than 30 programs nationwide that
work to educate African-American women about early detection for
breast cancer. She took her questions to Witness Project co-founder
Deborah Erwin, director of the Office of Cancer Health Disparities
Research in the Division of Cancer Prevention and Population
Sciences at Roswell Park Cancer Institute (RPCI). Citing her
family’s breast cancer history, Meadows-Ray proposed a study
that would look for new genetic mutations related to breast cancer
common in, or even unique to, African-American families.

Erwin proposed the idea to genetic epidemiologist Heather Ochs-Balcom of the UB School of Public
Health and Health Professions, and Ochs-Balcom (PhD ’04)
turned it into “Jewels in Our Genes,” a nationwide
research project conducted between 2009 and 2014. Led by
Ochs-Balcom and funded by Susan G. Komen for the Cure, the study
involved 106 families from across the U.S. and researchers from
UB’s school of public health, Roswell Park, Case Western
Reserve University School of Medicine in Cleveland, and the Icahn
School of Medicine at Mount Sinai Hospital in New York.

The team recently announced its first discovery: Study
participants with breast cancer carry segments of DNA that were
previously unknown and that are not carried by their female
relatives who don’t have breast cancer.

“This is a very exciting finding,” says Ochs-Balcom,
who published the results in the journal Cancer Epidemiology,
Biomarkers & Prevention in February. “Now that
we’ve found the new genomic regions, we can search them for
chromosomal mutations that cause the disease and try to learn if
the mutations are unique to African-Americans.”

Ochs-Balcom points out that young African-American women are at
higher risk of premenopausal breast cancers than others in their
age group. Early-onset cancers and aggressive, difficult-to-treat
cancers (like triple negative) are also much more common in
African- American women than in other groups. If a genetic mutation
is responsible, its discovery would facilitate early detection and
treatment for women in at-risk families, which would go a long way
toward improving outcomes for those with the gene.

Part of the reason this research hasn’t been done until
now, says Ochs-Balcom, is that family studies—the best way to
discover genetic anomalies—are difficult; they require a
considerable time commitment by multiple family members. This study
was made possible by a multipronged recruitment approach involving
informed, supportive community partners.

“Across the country, community organizations and
individuals like Veronica personally encouraged friends, neighbors
and family members to take part,” Ochs-Balcom says, adding
that volunteers were especially good at conveying the urgency and
importance of this work. Indeed, this community recruitment
methodology was so successful, it was presented at the 2014 annual
meeting of the American Association for Cancer Research.

Ochs-Balcom says she cannot stress enough the critical role
played by Meadows-Ray in making this paradigm-shifting research
happen. “Whatever success we realize,” she says,
“I want to emphasize that this study—the first of its
kind—started with her.”